PubMed Health⌕ Search

Biomedical subjects

S Law

Publications and source records attributed to S Law.

At least 37 records · Page 2Linked to original sources
PubMed2001

Telomerase activity in small cell esophageal carcinoma.

Small cell carcinoma of the esophagus is a rare and aggressive malignant tumor. Telomerase activation is common in human cancers. There is a lack of data on telomerase activity in esophageal small cell cancers. The present report studied the role of telomerase activity in esophageal small cell carcinoma. The clinicopathologic data of five patients with small cell carcinoma of the esophagus who underwent primary surgical treatment between 1991 and 2000 were studied. Telomeric repeat amplification protocol assays were used to investigate telomerase activity in these tumors. The proliferative activity (MIB-1) and p53 expression of these tumors were also studied using immunohistochemistry and correlated with the telomerase activity. All five small cell carcinomas showed detectable telomerase activity in the primary tumor. Two out of the five morphologically normal esophageal mucosae adjacent to the primary tumor had detectable telomerase activity. There was no correlation between the p53 expression, tumor stage, survival of patients, and the presence of telomerase activity. High MIB-1 expression in esophageal small cell carcinomas was associated with high telomerase activity. Telomerase activation is common in small cell carcinoma of the esophagus. This fact may find application in anti-telomerase treatment for this aggressive tumor.

Antigens, Nuclear↗
PubMed2001

Analysis of reduced death and complication rates after esophageal resection.

OBJECTIVE: To identify factors that have contributed to reduced rates of death and complications after esophageal resection in a 17-year period at a tertiary referral center. SUMMARY BACKGROUND DATA: There has been an evolving refinement in surgical technique and perioperative management of patients undergoing esophageal resection at Queen Mary Hospital during the past two decades. As of the end of 1998, there had been no hospital deaths among the last 105 consecutive resections performed for esophageal squamous cancer. METHODS: The results of esophageal resection for squamous cell carcinoma were analyzed using a prospective esophageal database. A longitudinal study was performed to compare and analyze rates of death and complications for three consecutive time periods. RESULTS: The study group comprised 710 patients who underwent one-stage esophageal resection between 1982 and 1998. A transthoracic esophagectomy was the preferred approach in 590 patients (83%). The overall hospital death rate was 11%. The leading causes of hospital death were pulmonary complications (45.5%) and progression of malignant disease (21.5%); anastomotic leakage accounted for 9% of deaths. During the study period, the hospital death rate decreased from 16% to 3.2%, and the incidence of postoperative respiratory failure decreased from 15.5% to 6.5%. Perioperative factors that correlated with the decreased death rate over time were the increased postoperative use of epidural analgesia and bronchoscopy (for clearance of pulmonary secretions), a decrease in history of smoking, and a decrease in surgical blood loss of more than 1,000 mL. CONCLUSIONS: In this series of predominantly transthoracic esophagectomies, there has been a decline in the hospital death rate to less than 5%. These results are largely attributable to factors aimed at reducing postoperative pulmonary complications.

Aged↗
PubMed2001

Esophageal cancer.

Accurate pretherapy staging for esophageal cancer is important for stage-directed therapy. Precise staging is also essential for quality control and ensuring the validity of clinical trials. Endoscopic ultrasound is currently the best technique in local regional staging. Various investigators have attempted to overcome the problems of nontraversable lesions and restaging after neoadjuvant therapy. Positron emission tomography scan was shown to be especially useful in identifying distant metastases. Its more widespread use is likely to impact on treatment strategies. Surgical resection remains the mainstay of treatment of esophageal cancer. Improvement in immediate postoperative morbidity, mortality, and long-term survival was shown by various reports to relate to experience and volume. The concept of three-field dissection was further defined by illustrating the importance of lymphadenectomy around the recurrent laryngeal nerves. Multimodality treatments continue to receive attention. Several studies have established the patterns of practice in the United States in treating esophageal cancer. Chemoradiation programs are gaining a more important role and are widely used, although their exact roles are uncertain. Closely related to this area of research is the search of molecular markers of favorable response to such therapies. Concerning palliative treatment for esophageal cancer, self-expanding metallic stents have a definite role in patients with malignant dysphagia. Their results and complications are reviewed. Lastly, quality-of-life issues have assumed more importance in studies in oncology. Prospective quality-of-life data should be evaluated in future studies on different treatment methods for this deadly disease.

Journal Article↗
PubMed2001

Detection of genetic alterations in esophageal squamous cell carcinomas and adjacent normal epithelia by comparative DNA fingerprinting using inter-simple sequence repeat PCR.

In this study, we screened 19 esophageal squamous cell carcinomas (ESCCs) for the detection of genetic alterations using inter-simple sequence repeat PCR, a DNA fingerprinting approach. Three simple repetitive unanchored primers representing tri- and tetranucleotide repeats [(GTG)(5), (GACA)(4), and (GATA)(4)] were used, and evidence of gains and losses of chromosomal sequences were detected in all tumors (19 of 19 cases) for at least one of the primers. In 13 of these cases, apparently normal marginal epithelia adjacent to the tumors were also collected and examined. Eight of the 13 (62%) patients showed matching somatic mutations in the marginal epithelia adjacent to the tumors. Five of these 8 (63%) marginal epithelial samples were histologically normal, two were dysplastic, and one had extremely rare tumor cells. In 3 of these 13 (23%) cases, the profile bands were also seen to quantitatively increase in intensity, progressing from normal epithelia to marginal epithelia to tumors. Ten profile bands showing gains and one profile band showing loss in tumors compared with the corresponding normal epithelia were cloned, and their origins were determined by sequencing. The DNA sequence of one of the profile bands showing gain in the tumor could be matched to an expressed sequence tag sequence that has been mapped to the 7q22 region, a genomic amplification novel to ESCC. The sequence of the other profile band showing gain in the tumor could be matched to a nonexonic sequence of chromosome 20, whereas the sequences of the remaining profile bands could not be matched with any known sequences after comparison with the genomic sequence data in the European Molecular Biology Laboratory and GenBank databases. The bona fide nature of the gains or losses of 11 profile bands in the original cases was confirmed by direct genomic PCR amplification. The frequencies of these specific gene alterations in tumors were then analyzed in a total of 60 ESCCs, which included 41 additional cases of ESCC. Significantly, 26 of 60 (43%) tumors showed the DNA amplification for the expressed sequence tag sequence of chromosome 7, whereas the frequency of other individual gene alterations ranged from 7% to 15%. It is concluded that the inter-simple sequence repeat PCR strategy is adequate for the detection of somatic mutations in tumors, most of which are quantitative alterations in anonymous genomic sequences. This approach is also suitable for detection of somatic mutations preceding the onset of morphologically detectable neoplasia in ESCC.

Aged↗
PubMed2001

Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC.

PURPOSE: This study aims to identify differentially expressed genes in esophageal squamous cell carcinoma (ESCC) through the use of a membrane-based cDNA array. EXPERIMENTAL DESIGN: Two newly established human ESCC cell lines (HKESC-1 and HKESC-2) and one corresponding to a morphologically normal, esophageal epithelium tissue specimen, prospectively collected from the HKESC-2-related patient, were screened in parallel using a cDNA expression array containing gene-specific fragments for 588 human genes spotted onto nylon membranes. RESULTS: The results of cDNA expression array showed that 53 genes were up-regulated 2-fold or higher and 8 genes were down-regulated 2-fold or higher in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of a subset of these differentially expressed genes gave results consistent with cDNA array findings. Four of the differentially expressed genes that belong to the categories of oncogenes/tumor suppressor genes (Fra-1 and Neogenin) and cell cycle-related genes (Id-1 and CDC25B) were studied more extensively for their protein expression by immunohistochemistry. The two ESCC cell lines and their corresponding primary tissues, 61 primary ESCC resected specimens and 16 matching, morphologically normal, esophageal epithelium tissues were analyzed. The immunostaining results showed that Fra-1, Neogenin, Id-1, and CDC25B were overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the microarray findings. The results of the clinical specimens showed that the Fra-1 gene was overexpressed in ESCC compared with normal esophageal epithelium in 53 of 61 cases (87%), Neogenin in 57 of 61 cases (93%), Id-1 in 57 of 61 cases (93%), and CDC25B in 48 of 61 cases (79%). Furthermore, the expression of Fra-1, Neogenin, and Id-1 in ESCC correlated with tumor differentiation. CONCLUSIONS: Overall, this study demonstrates that multiple genes are differentially expressed in ESCC and provides the first evidence that oncogenes Fra-1 and Neogenin and cell cycle-related genes Id-1 and CDC25B are overexpressed in ESCC.

Carcinoma, Squamous Cell↗
PubMed2001

Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC.

PURPOSE: To examine the global gene expression of cancer-related genes in esophageal squamous cell carcinoma (ESCC) through the use of Atlas Human Cancer Array membranes printed with 588 well-characterized human genes involved in cancer and tumor biology. EXPERIMENTAL DESIGN: Two human ESCC cell lines (HKESC-1 and HKESC-2) and one morphologically normal esophageal epithelium tissue specimen from the patient of which the HKESC-2 was derived were screened in parallel using cDNA expression arrays. The array results were additionally validated using semiquantitative PCR. The overexpression of oncogene MET was studied more extensively for its protein expression by immunohistochemistry in the two ESCC cell lines and their corresponding primary tissues and 61 primary ESCC resected specimens. Sixteen of these 61 ESCC cases also had available the corresponding morphologically normal esophageal epithelium tissues and were also analyzed for MET expression. The clinicopathological features associated with overexpression of the MET gene were also correlated. RESULTS: The results of cDNA arrays showed that 13 cancer-related genes were up-regulated > or =2-fold (CDC25B, cyclin D1, PCNA, MET, Jagged 2, Integrin alpha3, Integrin alpha6, Integrin beta4, Caveolin-2, Caveolin-1, MMP13, MMP14, and BIGH3) and 5 genes were down-regulated > or =2-fold (CK4, Bad, IGFBP2, CSPCP, and IL-1RA) in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of 9 of these differentially expressed genes, including the MET gene, gave results consistent with cDNA array findings. The immunostaining results of the expression of MET gene showed that MET was overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the cDNA arrays findings. The results of the clinical specimens showed that the MET gene was overexpressed in ESCC compared with normal esophageal epithelium in 56 of 61 cases (92%). Moreover, the overexpression of MET protein was more often seen in well/moderately differentiated than in poorly differentiated ESCC. CONCLUSIONS: Multiple cancer-related genes are differentially expressed in ESCC, the oncogene MET is overexpressed in ESCC compared with normal esophageal epithelium, and its protein overexpression correlates with tumor differentiation in ESCC.

Aged↗
PubMed2000

Pyloroplasty in gastric replacement of the esophagus after esophagectomy: one-layer or two-layer technique?

Pyloroplasty is our routine drainage procedure performed when the stomach is used as the esophageal substitute after esophageal resection for cancer. The technique of pyloroplasty varies among surgeons and effectiveness has not been studied. Thirty-four patients with a gastric conduit whose pyloroplasty was constructed with a one-layer technique (group 1) were compared with a historical cohort of 31 patients treated with a two-layer method (group 2). Patients who had an abnormal pyloroduodenal region were excluded from the study. Perioperative morbidity and post-operative gastrointestinal symptoms within the first 6 months were evaluated. Patient demographics and the types of surgical procedures did not differ between the two groups. The median daily output from the nasogastric tube was 119 mL in group 1 and 115 mL in group 2 (p = 0.49). In 40 out of 65 patients (62%), the nasogastric tube was removed at a median of 3 days after the operation in both groups. There was no leakage from the pylorus or the esophagogastric anastomosis in this study. In both groups, the patients could resume a semisolid diet at a median of 8 days after surgery. One patient in group 1 and two patients in group 2 developed gastroparesis clinically. No patient, however, required reoperation. There was no significant difference in cardiopulmonary complications attributable to the technique of pyloroplasty. The incidence of gastrointestinal symptoms within the first 6 months after surgery did not differ. Regurgitation was the most common symptom, affecting 10 patients in each group, 29% and 32% in group 1 and group 2 respectively (p = 1.0). Pyloroplasty was an effective gastric drainage procedure after esophagectomy whether the one or two-layer method was used. The authors prefer the one-layer method, which is safe and simple.

Anastomosis, Surgical↗
PubMed2000

Esophageal cancer.

Papers published in the English literature on esophageal cancer in 1999 were retrieved by a MEDLINE search. Selective publications were reviewed in light of current knowledge. Many studies were performed to refine staging methods of esophageal cancer, especially in the use of endoscopic ultrasound. Although better designs have overcome the problem of nontraversable tumors, its use in staging after neoadjuvant therapies remains suboptimal. Important studies on various surgical techniques were reported, including randomized trials on different routes of reconstruction after esophageal extirpation, and the updated results of transhiatal resections. In contrast to the minimalist approach of transhiatal resection, investigators from both East and West have also described the pathologic basis of lymphatic spread of esophageal cancer and its implications, favoring more radical lymphadenectomy. Another avenue that was explored is the use of neoadjuvant therapies to improve outcome. Different regimens were studied, and many papers focused on the molecular prediction of favorable response to such therapies. Overenthusiastic adoption of multimodality treatments is cautioned, however, in that they have not been validated. Further work is much needed in this area of research.

Journal Article↗
PubMed2000

Evaluation of single nucleotide polymorphism typing with invader on PCR amplicons and its automation.

Large-scale pharmacogenetics and complex disease association studies will require typing of thousands of single-nucleotide polymorphisms (SNPs) in thousands of individuals. Such projects would benefit from a genotyping system with accuracy >99% and a failure rate <5% on a simple, reliable, and flexible platform. However, such a system is not yet available for routine laboratory use. We have evaluated a modification of the previously reported Invader SNP-typing chemistry for use in a genotyping laboratory and tested its automation. The Invader technology uses a Flap Endonuclease for allele discrimination and a universal fluorescence resonance energy transfer (FRET) reporter system. Three hundred and eighty-four individuals were genotyped across a panel of 36 SNPs and one insertion/deletion polymorphism with Invader assays using PCR product as template, a total of 14,208 genotypes. An average failure rate of 2.3% was recorded, mostly associated with PCR failure, and the typing was 99.2% accurate when compared with genotypes generated with established techniques. An average signal-to-noise ratio (9:1) was obtained. The high degree of discrimination for single base changes, coupled with homogeneous format, has allowed us to deploy liquid handling robots in a 384-well microtitre plate format and an automated end-point capture of fluorescent signal. Simple semiautomated data interpretation allows the generation of approximately 25,000 genotypes per person per week, which is 10-fold greater than gel-based SNP typing and microsatellite typing in our laboratory. Savings on labor costs are considerable. We conclude that Invader chemistry using PCR products as template represents a useful technology for typing large numbers of SNPs rapidly and efficiently.

Base Sequence↗
PubMed2000

Increased exhaled nitric oxide in chronic bronchitis: comparison with asthma and COPD.

STUDY OBJECTIVES: To test the hypothesis that exhaled nitric oxide (NO) is increased in patients with chronic bronchitis, and to compare the results with exhaled NO in patients with asthma and COPD. STUDY DESIGN: Cross-sectional survey. SETTING AND PATIENTS: Veterans Administration pulmonary function laboratory. Patients (n = 179) were recruited from 234 consecutive patients. Two nonsmoking control groups of similar age, with normal spirometry measurements and no lung disease, were used (18 patient control subjects and 20 volunteers). MEASUREMENTS: Participants completed questionnaires and spirometry testing. Exhaled NO was measured by chemiluminescence using a single-breath exhalation technique. RESULTS: Current smoking status was associated with reduced levels of exhaled NO (smokers, 9. 2 +/- 0.9 parts per billion [ppb]; never and ex-smokers, 14.3 +/- 0. 6 ppb; p < 0.0001). Current smokers (n = 57) were excluded from further analysis. Among nonsmokers, the levels of exhaled NO were significantly higher in patients with chronic bronchitis (17.0 +/- 1. 1 ppb; p = 0.035) and asthma (16.4 +/- 1.3 ppb; p = 0.05) but not in those with COPD (14.7 +/- 1.0 ppb; p = 0.17) when compared with either control group (patient control subjects, 11.1 +/- 1.6 ppb; outside control subjects, 11.5 +/- 1.5 ppb). The highest mean exhaled NO concentration occurred in patients with both chronic bronchitis and asthma (20.2 +/- 1.6 ppb; p = 0.005 vs control subjects). CONCLUSIONS: Exhaled NO is increased in patients with chronic bronchitis. The increase of exhaled NO in patients with chronic bronchitis was similar to that seen in patients with asthma. The highest mean exhaled NO occurred in patients with both chronic bronchitis and asthma. Exhaled NO was not increased in patients with COPD. Although chronic bronchitis and asthma have distinct histopathologic features, increased exhaled NO in patients with both diseases suggests common features of inflammation.

Asthma↗
PubMed2000

Esophageal small cell carcinomas: clinicopathologic parameters, p53 overexpression, proliferation marker, and their impact on pathogenesis.

OBJECTIVE: To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma. METHOD: Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made. RESULTS: Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810-964) positive cells per 1000. Overall median survival was 3.4 months. In patients who underwent chemotherapy, there was significant response. CONCLUSIONS: Esophageal small cell carcinoma is an aggressive tumor. Overexpression of p53 is associated with early stages of carcinogenesis. The high proliferative index, as defined by the MIB-1 immunohistochemical method, may be related to aggressive behavior and high sensitivity to chemotherapy and radiotherapy.

Adult↗
PubMed2000

Human TCR as antigen: homologies and potentially cross-reactive HLA-DR2-restricted epitopes within the AV and BV CDR2 loops.

The major function of the T-cell receptor is to confer antigen specificity to T cells. However, nascent TCR proteins that are not assembled into functional heterodimers may be processed and displayed with self MHC molecules on the T-cell surface, and are thought to be the genesis of autoregulatory T cells that can limit inflammatory responses through T-T network interactions. In previous work, we and others have exploited this natural regulatory system using TCR peptides to amplify regulatory T cells that potentially can treat human autoimmune diseases such as multiple sclerosis (MS) and arthritis. The development of this approach is limited by the diversity of human TCR V gene sequences, and by lack of knowledge of exactly which regions of the V gene proteins are immunogenic in association with various MHC alleles. To identify similar amino acid sequences within and among human V gene families that might have immunologic cross reactivity, we aligned 74 known AV and 109 known BV protein sequences into homologous groups using the ClustalX program. Moreover, with a focus on CDR2 peptides that have previously been used to induce regulatory T cells in clinical trials, we established homologous peptide groups, and then identified the optimal amino acid motifs for binding to two alleles, HLA-DRB1*1501 and DRB5*0101, that have been associated with susceptibility to MS. From this analysis, > 75% of AV and BV CDR2 sequences were predicted to bind with at least moderate avidity to each of the DR2 alleles, thus enhancing the likelihood that they could be antigenic. Further ordering of putative TCR contact residues revealed a different set of homology groupings, including many intrafamily sequence matches and some interfamily matches that might allow immunological cross reactivity. Particularly striking were DRB1*1501-restricted IH-S and IY-S motifs shared by BV11, BV12, and BV13 and BV3, BV12, BV13, and BV17 family members, respectively, and DRB5*0101-restricted RL-H and RL-Y motifs shared by BV11, BV12, and BV13 and BV13 and BV17 family members, respectively. This analysis may be useful in designing an array of clinically useful homologous peptides with optimal MHC binding properties and highly cross-reactive TCR binding motifs.

Alleles↗
PubMed1999

Esophageal carcinoma in a patient with bleeding esophageal varices.

More than 20 cases of esophageal carcinoma have been reported to develop after endoscopic injection sclerotherapy (EIS), and this technique is implicated in the pathogenesis of esophageal cancer. We report a case of esophageal carcinoma presenting as a superficial ulcer in a patient with esophageal varices with no prior EIS. Whether the development of esophageal carcinoma in patients with previous EIS is coincidental or consequential is controversial. Such carcinoma might have already existed before EIS in some reported cases. A causal relationship between EIS and esophageal carcinoma cannot be established without further clarification by a well-designed study.

Adenocarcinoma↗
PubMed1999

Malignant melanoma of the oesophagus: clinicopathological features, lack of p53 expression and steroid receptors and a review of the literature.

AIMS: Fortunately, primary malignant melanoma of the oesophagus is a rare entity. The aims of this study were to evaluate the clinicopathological features, p53 over-expression and steroid receptors in oesophageal melanomas and to review the reported cases in the literature. METHODS: Melanomas reported during a 15-year period (1982-1996) in the Queen Mary Hospital were studied. The clinicopathological features and survival data of patients with oesophageal melanomas were noted. Representative tissue was collected from each tumour and immunohistochemical preparations for HMB-45, p53, oestrogen and progesterone receptors were made. A review of oesophageal melanomas reported in the literature was also performed. RESULTS: Three cases of primary malignant melanoma of the oesophagus were found. They accounted for 3% of melanomas and 0.2% of oesophageal cancers diagnosed. The melanomas were fusiform and large at the time of resection. All three patients died of their malignancy within 9 months of operation. The tumours stained positive for HMB-45 and were negative for p53, oestrogen and progesterone receptors. From previous reports, 154 oesophageal melanomas were documented. The tumours were fusiform, large, often pigmented and located in either the middle or lower oesophagus. Although many oesophageal melanomas presented at early stages (stages I or II), their biological behaviour was aggressive. The 5-year survival rate was 5.7%. CONCLUSIONS: Melanoma of the oesophagus is an aggressive tumour. There is no evidence for the p53 gene and female sex hormones having a role in the development or progression of the tumour.

Aged↗
PubMed1999

The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients.

OBJECTIVE: The p21 gene is thought to play a central role in tumor suppression. The aim of this study was to examine the clinicopathological role of p21 and p53 in esophageal squamous cell carcinomas. METHODS: The expression of p21 and p53 proteins in 153 Chinese patients (131 men, 22 women) with resected esophageal squamous cell carcinomas was investigated by the immunohistochemical method. Correlation between p21 and p53 expression and clinicopathological features was examined. RESULTS: The expression of p21 and p53 was detected in 70% and 64% of the tumors, respectively. The staining of p21 and p53 was also found in squamous carcinoma in situ, dysplasia, and nontumor epithelium. p21 expression was often weak in the suprabasal cells and found in better differentiated tumors. There was no significant correlation between the expression of p21 and the abnormal accumulation of p53. The prognosis of the patients depended on the size, stage, and p21 expression of the lesion. In stage III lesions with tumor diameter < or = 7.5 cm (n = 93), patients with loss of p21 expression had better survival. The survival rates of patients were worse if they had expression of both p21 and p53. CONCLUSIONS: Thus, p21 and p53 had prognostic value for esophageal squamous cell carcinomas. Loss of p21 expression was shown without p53 alternations, indicating that other mechanisms are also involved in turning off the gene. The pattern of p21 and p53 expression predicts an aggressive clinical course of esophageal squamous cell carcinomas.

Actuarial Analysis↗